Nitrosyl-cobinamide (NO-Cbi), a new nitric oxide donor, improves wound healing through cGMP/cGMP-dependent protein kinase

Abstract

a b s t r a c t a r t i c l e i n f oNitric oxide (NO) donors have been shown to improve wound healing, but the mechanism is not well defined. Here we show that the novel NO donor nitrosyl-cobinamide (NO-Cbi) improved in vitro wound healing in several cell types, including an established line of lung epithelial cells and primary human lung fibroblasts. On a molar basis, NO-Cbi was more effective than two other NO donors, with the effective NO-Cbi concentration ranging from 3 to 10 μM, depending on the cell type. Improved wound healing was secondary to increased cell migration and not cell proliferation. The wound healing effect of NO-Cbi was mediated by cGMP, mainly through cGMPdependent protein kinase type I (PKGI), as determined using pharmacological inhibitors and activators, and siRNAs targeting PKG type I and II. Moreover, we found that Src and ERK were two downstream mediators of NO-Cbi's effect. We conclude that NO-Cbi is a potent inducer of cell migration and wound closure, acting via cGMP, PKG, Src, and extracellular signal regulated kinase (ERK).

A Novel, Direct NO Donor Regulates Osteoblast and Osteoclast Functions and Increases Bone Mass in Ovariectomized Mice

“…(10,30,32) Here, we examined the skeletal effects of a novel NO donor, nitrosylcobinamide (NO-Cbi), derived from the vitamin B 12 precursor cobinamide; it releases NO directly, without biotransformation or generation of reactive oxygen species. (33)(34)(35)(36) We found that NO-Cbi enhanced trabecular bone mass in intact and OVX mice by enhancing osteoblast activity and inhibiting osteoclast differentiation.…”

Combination of low level light therapy and nitrosyl-cobinamide accelerates wound healing

“…In separate work, we demonstrated that LLLT and nitrosylcobinamide (NO-Cbi) increased wound healing. 19,20 Here, we demonstrate that the combination of LLLT and NO-Cbi produces much greater wound healing than either treatment alone. In addition, we show that the functional response of each modality proceeds through a different biochemical pathway: the electron transport chain and cGMP, respectively, with both resulting in ERK1/2 (extracellular signal-regulated kinase) activation.…”

“…1(a) and 1(b)]. 19,20 We now show that combining NO-Cbi and LLLT markedly enhanced wound healing compared to either treatment alone [Figs. 1(a) and 1(b)].…”

“…The scratch wound closure assay has been previously described. 19 Briefly 600 to 700-μm-wide single-line scratches were mechanically generated in a cell monolayer by a 200-μl plastic tip (∼450 to 600 μm at the tip) across the length of the well. Multiple images were acquired along the length of the scratch to ensure representative sampling areas for each gap.…”

Studies on the Reduction of Dehydroascorbic Acid by Glutathione in the Presence of Aquahydroxocobinamide

“…The absence of 5,6‐dimethylbenzimidazole provides Cbi‐enhanced ligand binding and redox properties , . Cbi complexes are investigated as antidotes of cyanide, hydrogen sulfide, hypotensive, and wound‐healing drugs as well as cyanide and hydrogen sulfide sensors.…”